Download Pharmacokinetics Demonstrating Sustained Dexamethasone

Pharmacokinetics Demonstrating Sustained Dexamethasone Delivery
from a Punctum Plug in a Canine Model
Author Block: A. Desai, C. Blizzard, M. McGrath, M. Bassett, P. Jarrett, A. Driscoll, A. Sawhney.
All of Ocular Therapeutix, Inc., Bedford, MA
Purpose: To examine the dose-dependent pharmacokinetics of dexamethasone delivered
from a biodegradable hydrogel punctum plug in a canine model.
Methods: Micronized dexamethasone (Dex) was suspended in a multi-arm PEG solution at
two different levels (high and low dose) and injected into small bore tubing prior to crosslinking. Fluorescein was conjugated into the hydrogel to aid plug visualization through the
tissue using the blue light from a slit lamp. The Dex hydrogel matrix was dried and cut into
punctum plugs. The Dex plugs were inserted into the inferior canaliculus of beagles and a
subset was removed each week for imaging. Tear fluid samples were collected at weekly
intervals and dexamethasone concentration was determined by LC/MS. The high dose was
evaluated in a toxicology study and
the low dose is a clinically
representative dose designed for
four weeks of tapered release that
was assessed in a PK study.
Results: The Dex plug demonstrated
a sustained drug release profile in
tear fluid with a tapering effect over
the treatment period. Explanted
plugs (Figure Two) of the low dose
formulation illustrate the drug
release over time, with full drug
clearance from the plug at four
weeks.
Conclusions: Topical
corticosteroids, such as
dexamethasone, are used to treat
inflammation for various ophthalmic
conditions including post-operative
inflammation. Many therapies
require multiple daily administrations (up to hourly for severe conditions) for the first
several weeks followed by tapering to a lesser frequency as the inflammation subsides and
the condition resolves. A single-dose dexamethasone punctum plug which biodegrades
may provide a more convenient option to help eliminate patient compliance with stringent
dosing requirements, and help ensure appropriate treatment and resolution of the
condition.